The present invention relates to biocompatible non-woven fibrous materials having a nano-micro topography, which may be used to cover implantable medical devices and to fabricate three-dimensional drug-eluting materials, and methods for producing such materials.
Non-woven materials made from synthetic or natural polymers are used in various applications, including tissue engineering, clinical diagnostics, wound healing, drug delivery, and medical implants. Such materials may be employed, among others, to produce vascular grafts for supporting a weakened artery and covered stents which inhibit tissue growth into the stents. Vascular grafts and covered stents generally consist of a support structure and a cover surrounding it. The support structure is typically a mesh cylindrical device that fits into the opened artery and is radially expanded against the walls of the artery.
It is known to fabricate non-woven materials using a process by which polymer fibers are produced by means of an electrostatically driven jet of polymer solution, referred to as electrospinning. Electrospinning is however a rather complex and time-consuming manufacturing process, which requires applying a high voltage and provides insufficient control of material homogeneity and reproducibility. In particular when small fibers, such as nanosize fibers, are produced the total yield of the electrospinning process is very low and process scale-up cannot be easily achieved. FIG. 1A represents a scanning electron microscopy (SEM) image of a portion of an electrospun material known by the prior art, which has been analyzed to obtain quantitative information on the surface features. Referring to FIG. 1B, it can be seen that the material is comprised of long spaghetti-like fibers having various thicknesses of about one to four microns and has a rather inhomogeneous randomized pattern with pores ranging from one to twelve microns.
Since implantable medical devices will often provoke adverse body reactions, a therapeutic agent may be applied to the devices to improve the biocompatibility and/or treat diseases by delivering the therapeutic agent directly to the target site. However, incorporation of drugs into the polymer will not ensure a controlled drug distribution as schematically visualized in FIG. 2. A therapeutic agent 137 may not be homogeneously distributed within a composition 126 comprising one or more polymers 140 and therapeutic agents 137 due to particle sedimentation, particle aggregation, and the like. This can result in an inhomogeneous distribution of the therapeutic agent within the produced material and may have a negative impact on the performance of the specific drug delivery product.